EP1339397B1 - Absorbing agents and cover layer which is impermeable to active substances and which contains channel-formers or removable protective layer of a transdermal therapeutic system - Google Patents

Abstract

This present invention concerns a cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system, comprising a thermoplastic film which either directly contains the absorbing agents and channel-forming agents or is coated with a polymer support (thermoplast) containing these substances. The polymer support can either be applied over the entire surface of the film or in patterns, directly during production. The thermoplastic film that is used and the polymer support can be made from either the same or different materials.

Description

The invention relates to a drug-impermeable Top layer or a removable protective layer of a transdermal therapeutic system, the absorbent and contains channel formers.

Those in conventional transdermal therapeutic systems cover layers used are foils made of acetal, acrylate, Acrylonitrile butadiene styrene, acrylonitrile (methyl methacrylate) Copolymer, acrylonitrile copolymer, Ethylene ethyl acrylate, ethylene methyl acrylate, Ethylene vinyl acetate, ethylene vinyl acetate copolymer, Ethylene vinyl alcohol polymer, ionomers, nylon (polyamide), Nylon copolymer, polybutylene, polycarbonate, polyester, Polyethylene terephthalate, thermoplastic polyester copolymer, Polyethylene copolymer (high density), polyethylene (high-molecular-weight, high-density), polyethylene (intermediate-molecular-weight, high-density), polyethylene (linear low density), polyethylene (low density), polyethylene (medium density), polyethylene oxide, polyimide, polypropylene, Polypropylene (coated), Polypropylene (oriented), Polystyrene, Polyurethane, polyvinyl acetate, polyvinyl chloride, Polyvinylidene chloride and / or styrene acrylonitrile, which at Metallized or pigmented as needed. They have the task of stabilizing the active ingredient-containing system and protect it from outside influences. The top layer is impermeable to active substances and thus prevents diffusion of the active ingredient to the outside.

Those used in transdermal therapeutic systems peelable protective layers are also impermeable to active substances and usually consist of Polyester, polyethylene, polypropylene, polysiloxane, Polyacrylate, ethylene vinyl acetate, polyurethane, polyisobutene or paper, mostly with silicone and / or polyethylene coated, or a composite of these. They have also the task of closing the active ingredient-containing system stabilize and protect against external influences. The peelable protective layer is impermeable to active ingredients and thus prevents diffusion of the active ingredient during the Storage to the outside.

Transdermal therapeutic systems are commonly used in Packaged sachets. The sachets usually consist of Aluminum coated composite material. Through this coating will the moisture and Reduced oxygen permeability of the packaging. The Permeability depends on the layer thickness. ever the thicker the aluminum coating, the more polluting and the production and disposal of the Packaging. Complete impermeability can, however practically cannot be achieved. That's why it is transdermal therapeutic system always a certain Exposed to moisture. In addition, there is the transdermal therapeutic systems after manufacturing a certain Residual moisture to the environment. To be a reasonable one Ensuring storage stability can be included in the sachet Be introduced inlay that contains a drying agent. The packaging of the transdermal therapeutic system this makes it more complex and much more expensive. Odor-intensive substances such as amines and polymer monomers during storage from the active ingredient or the Adhesive layer can be released with this Procedure not or only partially removed.

The object of the invention is the storage stability of transdermal therapeutic systems by increasing the negative influence of moisture, oxygen, free amines and / or free polymer monomers on the stability of the transdermal therapeutic systems to a minimum is reduced. The production of the transdermal therapeutic systems should be in the usual way and Way, without additional complex production steps, done, the cost of packaging in the same Trains are to be lowered.

The task according to the invention could now surprisingly can be solved by as an active ingredient-impermeable cover layer or peelable protective layer of the transdermal therapeutic system a polymer in the form of a film is used, either the absorbent and Channel formers directly or with one of these Polymer carrier containing substances is coated. The Coating can either cover the entire film or in samples (e.g. grid shape) directly during production be applied.

The Capitol Specialty Plastics company has several Patent applications (WO 00/17259, WO 00/17260, WO 00/16884, WO 99/62697, WO 99/61856, WO 98/39231, WO 99/61855, WO 00/17258, WO 99/63288, US 5,911,937), the polymers claim which absorbent, releasing Contain substances, channel formers, etc. These polymers will mainly for removing moisture in Packaging used. They are either inlays before, which is inserted as an insert into the packaging or the packaging is lined with it. The Thickness of the inlays and coating films described is ≥ 400 µm. This has the disadvantage that these inlays or coatings an additional production step require and represent another cost factor.

Through the cover layer according to the invention or removable Protective layer can be the thickness of the aluminum coating Packaging can be greatly reduced. This is good for the environment and cheaper the packaging. The manufacturing process must cannot be changed. The state of the art The usual production can continue to be carried out. In addition, there is no need for an additional drying element in the Packaging to be inserted. The manufacturing cost of the TTS can thus be significantly reduced.

The transdermal therapeutic system (TTS) can last for a long time Stored at a stable time. Even under extreme Conditions such as in the tropics, this can be transdermal therapeutic system without additional elements for a long time Time without loss of stability. You can also TTS with moisture-unstable active ingredients without Stability problems are kept. It can be in these Cases even extend the storage period.

The active ingredient-impermeable cover layer and / or peelable protective layer of a transdermal therapeutic system consists of a polymer, (i) that either the absorbent and channel former directly includes or (ii) that with one containing these substances Polymer carrier is coated. The polymer carrier can either over the entire film or in Samples can be applied directly during production. is provided its own polymer carrier, so top layer and / or protective layer and the polymer carrier either consist of the same or different materials.

The for the mixture of polymer (for polymer carrier or Top layer and / or removable protective layer), Absorbents and channel formers used polymers can be thermoplastics; you can e.g. Polyolefins, such as Polyethylene and / or polypropylene, polyisoprene, Polybutadienes, polybutenes, polysiloxanes, polyamides, ethylene-vinyl acetate copolymers, Ethylene-methacrylate copolymers, Polystyrenes, polyesters, polyanhydrides, polyacrylate nitriles, Polysulfonates, polyester amides, polyacrylate esters, propylene-maleic anhydride, Polyethylene-maleic anhydride, Polyethylene urethanes, polyethylene ethyl vinyl alcohols, Polyethylene nylon and / or polyurethanes.

Furthermore, the polymer can be a crosslinkable Act polymer that can be thermally or radiation-crosslinked, is especially UV-crosslinkable. So it can be the polymer of Polymer carrier or the top layer and / or the peelable Protective layer can be networked. Is a separate polymer carrier provided, a thermally crosslinkable polymer can be cold or in the heat on the top layer and / or protective layer be applied while a radiation crosslinkable Polymer can be applied cold or hot. The Networking can take place after the respective order.

The polymer content is 10-90% by weight based on the Total weight of the mixture of polymer, channel former and Absorbents, regardless of whether it is directly as a film or used as a coating.

The channel formers used in the present invention hydrophilic substances such as polyglycols, Ethyl vinyl alcohols, glycerin, pentaerithritol, Polyvinyl alcohols, polyvinyl pyrrolidone, vinyl pyrrolidone, N-methylpyrrolidone, polysaccharides, saccharides and / or Be sugar alcohols. As polyglycols Polyethylene glycol and / or polypropylene glycol preferred. As Saccharides can e.g. Glucose, mannose, galactose and / or Fructose can be used. As sugar alcohols come e.g. Mannitol, sorbitol, hexitol, dulcitol, xylitol, ribitol and / or erythrol in question. Among polysaccharides e.g. Dextrins and / or hydrolyzed starch can be understood.

The content of channel formers can be 10-40% by weight, based on the total weight of the mixture of polymer, channel former and Absorbents.

There can be different types of absorbents in the Top layer or removable protective layer introduced become.

An embodiment according to the invention includes Desiccant as an absorbent. There are three different groups of desiccants.

One group includes chemical substances with water Form hydrates. Examples of such chemical substances can be anhydrous salts that tend to be water or Absorb moisture while maintaining a stable hydrate form. This reaction binds the moisture and their release through a chemical reaction prevented.

The second group of desiccants contains substances that are reactive. These substances react with water or Moisture by forming a new substance. The new formed substances are usually at low Temperatures stable. Only when using high energy their formation is reversible again. This kind of Desiccants are mainly used for drying Solvents and as a water-absorbing material Polymers that themselves in a moisture-reduced Condition must remain used.

The third group of desiccants binds moisture through physical absorption. The desiccant particles have a fine capillary structure so that the moisture is drawn into this capillary. The pore size of the capillary and the capillary density determine the absorption properties of the desiccant. Examples of this type of desiccant are molecular sieves, silicon gels, soils (e.g. Montmorilli earth), certain synthetic polymers (e.g. polymers used in baby diapers) and starches.
This group of desiccants is preferred because of its inertness and water insolubility.

A preferred embodiment according to the invention includes molecular sieves with a pore size of 3 as drying agent - 15 angstroms.

Another embodiment of the invention includes Silicon gel with a pore size of 24 angstroms.

Metals and Alloys such as Nickel, copper, aluminum, silver and / or gold, metal-coated particles, such as e.g. silver-coated copper, silver-coated nickel and / or silver-coated glass microspheres, inorganic Fabrics such as Barium titanium trioxide, strontium titanium trioxide, Silicon dioxide, aluminum oxide, zinc oxide, Titanium dioxide, manganese oxide, copper oxide, antimony oxide, molten silicon, amorphous molten silicon, Ion exchange resins, lithium-containing metal oxides, hollow glass microspheres, silicon solgel, titanium solgel and / or mixed titanium, carbon-based materials, such as e.g. Carbon, activated charcoal and / or Diamond powder, elastomers such as e.g. Polybutadiene and / or Polysiloxane, semi-metals and / or ceramic material be used.

The content of absorbent (s) can be 10 to 70% by weight, based on the total weight of the mixture of polymer, Channel formers and absorbents.

The content must not be too high, otherwise the top layer becomes brittle. If the salary is too low, it is Moisture protection not sufficient.

The absorbents incorporated into the polymer are evenly distributed in the polymer or the film. The channel formers introduced into the polymer form channels which run through the entire film or the applied pattern from the outside inwards. Oxygen, moisture or other undesirable substances can thus migrate from the external environment into the interior of the film or pattern and react with the absorbent in the interior of the film or pattern. The rate of absorption
is many times higher, since a larger number of absorbent particles can react with the undesirable substances than in the absence of the channel formers. Depending on the choice of the channel formers, finer and thus a larger number of channels with increased branching or larger, less branched channels can arise in a smaller number in the polymer. The finer the channels, the greater the rate of absorption for unwanted substances.

If desired, pharmaceutically acceptable ones Dyes in the mixture of polymer, channel former and Absorbents are given.

If the top layer or removable protective layer consists of a Foil with integrated channel formers and absorbents the thickness of the layer is 5-100 µm, in particular 15-40 microns, preferably 15 microns.

In the event that the top layer or peelable Protective layer consists of a conventional film that either over the entire surface or with the formation of a pattern a mixture of a polymer, channel formers and Absorbent is coated, the thickness can be any can be set. The only point to consider is the flexibility. It must be satisfactory Use of the transdermal therapeutic system guarantee.

The conventional for a top layer impermeable to active ingredients (4) film used can according to the invention on the top and / or The underside can be coated with the mixture (5).

The conventionally used for the peelable protective layer According to the invention, the film can be directed towards the outside Side are coated with the mixture.

Under a transdermal therapeutic system, a Patch understood. This patch can be a Act matrix or membrane system, which one drug-impermeable cover layer (4) and a removable Has protective layer (1). You can do both Layers with the channel formers and absorbents be provided or only one of the layers.

If a separate polymer carrier is provided, then for the peelable protective layer as conventional film polyester, Polyethylene, polypropylene, polysiloxane, polyacrylate, Ethylene vinyl acetate, polyurethane, polyisobutene or paper, mostly coated with silicone and / or polyethylene, or a combination of these.

If a separate polymer carrier is provided, the in conventional transdermal therapeutic systems cover layers used as foils made of acetal, acrylate, Acrylonitrile-butadiene-styrene, acrylonitrile (methyl Methacrylate) copolymer, acrylonitrile copolymer, ethylene Ethyl acrylate, ethylene methyl acrylate, ethylene vinyl acetate, Ethylene vinyl acetate copolymer, ethylene vinyl alcohol Polymer, ionomer, nylon (polyamide), nylon (polyamide) Copolymer, polybutylene, polycarbonate, polyester, Polyethylene terephthalate, thermoplastic polyester Copolymer, polyethylene copolymer (high density), polyethylene (high-molecular-weight, high-density), polyethylene (intermediate-molecular-weight, high-density), Polyethylene (linear low density), polyethylene (low density), Polyethylene (medium density), polyethylene oxide, polyimide, Polypropylene, polypropylene (coated), polypropylene (oriented), polystyrene, polyurethane, polyvinyl acetate, Polyvinyl chloride, polyvinylidene chloride and / or styrene acrylonitrile are used, which are metallized if necessary or can be pigmented.

According to one embodiment, the matrix patch consists of the active ingredient-impermeable cover layer (4), from one or several containing the active ingredient and / or permeation enhancer, self-adhesive matrix layer (s) (2) or one or more matrix layer (s) (13), which with a Pressure sensitive adhesive (10) are coated and a peelable Protective layer (1).

The medically customary matrix formers are used for the matrix such as polyacrylate, silicone, polyisobutylene, rubber, rubber-like synthetic homo-, co- or Block polymers, butyl rubber, styrene / isoprene copolymer, Polyurethanes, copolymers of ethylene, Polysiloxanes, styrene / butadiene copolymer or a Mixture of these as provided in the prior art are used.

Polydimethylsiloxane, polyacrylates, polyisobutylene, polyacrylate with C ₄ -C ₁₀ alkyl alcohol esters, polyurethane, polyvinyl ether, amine-resistant silicone in ethyl acetate or n-heptane, polyisobutylene / mineral oil or a mixture of these can be used as the adhesive.

Another embodiment of the invention sets Membrane system. This consists of the drug-impermeable cover layer (4), one drug-containing reservoir or a reservoir layer (12), a semipermeable membrane (11), an optional Pressure-sensitive adhesive layer (10) and a removable protective layer (1) .

The reservoir contains the active ingredient (s) and / or Permeation promoters, stabilizers, emulsifiers, Thickeners and / or conventional membrane system or Reservoir plaster aids. The reservoir or the Reservoir layer lies between the top layer and the Membrane. If necessary, methyl cellulose, Hydroxypropyl cellulose, hydroxyethyl cellulose, Carboxyvinyl polymer, sodium plyoxylate, Carboxymethyl cellulose or a mixture of these is used become.

The membrane, which is usually made of inert polymers, especially based on polypropylene, polyvinyl acetate, Polyamide, ethylene-vinyl acetate copolymers and / or Silicone, can, depending on the pore size Active ingredient release have a controlling effect.

For the pressure sensitive adhesive layer one can use a pressure sensitive one Adhesives, for example based on polyurethane, Polyisobutylene base, polyvinyl ether base, silicone base, Select polyacrylate base or a mixture of these.

The silicone-based adhesive can be silicone adhesive that is based on two main components: a polymer or adhesive, in particular polysiloxane, and a resin that increases the stickiness. The polysiloxane adhesive is usually prepared with a crosslinker for the adhesive, typically a high molecular weight polydiorganosiloxane, and with the resin to provide a three-dimensional silicate structure using an appropriate organic solvent. The admixture of the resin to the polymer is the most important factor in changing the physical properties of the polysiloxane adhesives; see. For example, Sobieski, et al., ed "Silicone Pressure Sensitive Adhesives," Handbook of Pressure Sensitive Adhesive Technology, ^2nd., pp. 508-517 (D. Satas, ed.), Van Nostrand Reinhold, New sive Technology, 2 ^nd ed., Pp. 508-517 (D. Satas, ed.), Van Nostrand Reinhold, New York (1989).

Another example of a pressure sensitive adhesive Silicon-based is trimethylated silicon dioxide, which with Polydimethylsiloxane with terminal trimethylsiloxy groups has been treated.

The polyacrylate-based adhesives can be any homopolymer, copolymer or terpolymer, act consisting of various acrylic acid derivatives.

The polyacrylate polymers can be one or more Monomers of acrylic acids and other copolymerizable Be monomers. The acrylate polymers can also be copolymers of alkyl acrylates and / or methacrylates and / or copolymerizable secondary monomers or monomers with include functional groups. If you change the amount any variety added as a monomer can use the cohesive properties of the resulting Acrylate polymers are changed. In general, there is Acrylate polymer from at least 50% by weight of an acrylate, Methacrylate, alkyl acrylate or alkyl methacrylate monomer, 0 to 20% of a functional monomer, copolymerizable with acrylate, and 0 to 50% of another monomer.

The following are various acrylate monomers such as e.g. Acrylic acid, methacrylic acid, butyl acrylate, butyl methacrylate, Hexyl acrylate, hexyl methacrylate, isooctyl acrylate, Isooctyl methacrylate, glycidyl methacrylate, 2-hydroxyethyl acrylate, Methyl acrylate, methyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decyl acrylate, Decyl methacrylate, dodecyl acrylate, dodecyl methacrylate, Tridecyl acrylate and tridecyl methacrylate, which are listed can be polymerized alone or in a mixture.

In addition, functional monomers that are compatible with the above mentioned acrylates are copolymerizable, such as for example acrylic acid, methacrylic acid, maleic acid, Maleic anhydride, hydroxyethyl acrylate, hydroxypropyl acrylate, Acrylamide, dimethylacrylamide, acrylonitrile, dimethylaminoethyl acrylate, dimethylaminoethyl tert-butylaminoethyl acrylate, tert-butylaminoethyl methacrylate, Methoxyethyl acrylate, vinyl acetate and methoxythyl methacrylate, for copolymerization be used.

Further details and examples of pressure-sensitive acrylates, which are suitable for the invention are ^nd ed in Sata's Handbook of Pressure Sensitive Adhesive Technology "Acrylic Adhesives", 2., Pp. 396-456 (D. Satas, ed.), Van Nostrand Reinhold, New York (1989).

The active ingredient contained in the transdermal therapeutic system can be, for example, a representative from the active ingredient group of corticoids, androgens, estrogens, progestogens, proton pump inhibitors, 5-HT ₁ antagonists, sympatholytics / sympathomimetics, anticholinergics, tranquillizers / anxiolytics, weaning agents, analgesics, calcium antagonists , Antiemetics, vasodilators, opiate antagonists, anticoagulants, antiparkinson agents, antidementants / cholinesterase inhibitors, ACE inhibitors, antihistamines, ulcer therapeutics / H ₂ receptor blockers, angiotensin II antagonists, neuroleptics, antidepressants and his or her anesthetics, loco.

The transdermal therapeutic system can be one or several representatives from the group of corticoids z. B. Beclomethasone, budesonide propionate, flunisolide acetate, Triamcinolone, fluticasone, betamethasone 17-valerate, Glycic acid, fluocortolone, beclomethasone dipropionate, Budesonide base, dexamethasone, hydrocortisone, flunisolide, Prednisone, triamcinolone acetonide, methylprednisolone, Betamethasone, deflazacort, cortisone, cortisone acetate, Prednylidene, cloprednol, fluocortolone-21-hexanoate, Prednicarbate and / or their derivatives and / or their pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of androgens e.g. Testosterone, testosterone undecanoate, androsterone and / or their derivatives and / or their pharmaceutically acceptable Contain salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of estrogens e.g. Estradiol, estradiol benzoate, estradiol valerate, Estradiol dipropionate, estrone, estriol, ethinyl estradiol, Diethylstilbestrol, diethylstilbestrol dimethyl ether, Diethylstilbestrol diphosphate, diethylstilbestrol dipropionate and / or their derivatives and / or their others pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of progestogens e.g. Progesterone, cyproterone acetate, cyproterone, chlormadinone, Chlormadinone acetate, medroxyprogesterone acetate, Levonorgestrel, norgestrel, norgestimate, norethiestrone acetate and / or their derivatives and / or their others pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of proton pump inhibitors e.g. Omeprazole, esomeprazole, lansoprazole, leminoprazole, Pantoprazole, Rabeprazole, Polaprezinc and / or their derivatives and / or their pharmaceutically acceptable salts as Active ingredient component included.

The transdermal therapeutic system can include one or more representatives from the group of migraine drugs or 5-HT ₁ antagonists, for example lisuride, sumatriptan, sumatriptan hydrogen succinate, rizatriptan, rizatriptan benzoate, almotriptan, avitriptan, eletriptan, frovatriptan, naratriptan and zolmitriptan and zolmitriptan / or contain their other pharmaceutically acceptable salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of sympatholytics / sympathomimetics e.g. Adimolol, adrenaline, albuterol, Alpenolol, Amosulalol, Arotinolol, Atenolol, Bambuterol, Betaxolol, Bevantolol, Bisoprolol, Bitolterol, Bopindolol, Broxaterol, Bucindolol, Bucumolol, Bufuralol, Bunitrolol, Bupranolol, butofilolol, carazolol, carbuterol, carteolol, Carvedilol, Cetamolol, Cicloprolol, Clenbuterol, Cloranolol, Crateolol, dihydroergotamine, dihydroergotamine tartrate, Dihydroergotamine mesylate, dilevalol, doxazosin, etilefrin, Epanolol, esatenolol, esmolol, fenetylline, fenoterol, Formoterol, ibuterol, isoprenaline, labetalol, landiolol, Levobetaxolol, levobunolol, levosalbutamol, mabuterol, Mepindolol, Metipranolol, Metoprolol, Morazon, Nebivolol, Nipradilol, norfenefrin, noradrenaline, oxprenolol, Penbutolol, picumeterol, pimolol, pindolol, pirbuterol, Phenmetrazine phenylephedrine, phentolamine, phenoxybenzamine, Prazosin, procaterol, propanolol, rimiterol, reproterol, Salbutamol, salmeterol, sotalol, sulfonterol, terazosin, Terbutaline, tertatolol, tienoxolol, tilisolol, timolol, Tolazoline, toliprolol, tolubuterol, tamsulosin, clonidine, Moxonidine and / or their derivatives and / or their pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of anticholinergics e.g. Ipratropium, oxitropium, atropine, scopolamine base, Ipratropium bromide, oxitropium bromide, atropine methyl bromide, Atropine methyl nitrate, atropine sulfate, atropine valerate, Scopolamine hydrobromide, scopolamine hydrochloride, Scopolamine hydroiodide, tropicamide, oxybutinin and / or their Derivatives and / or their other pharmaceutical contain harmless salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of Tranquillizers / anxiolytics e.g. Alprazolam, bentazepam, Bromazepam, camazepam, clorazepate, clonazepam, clotiazepam, Diazepam, etiracetam, etiolam, fludiazepam, flunitrazepam, Flurazepam, flutazolam, flutoprazepam, halazepam, ketazolam, Loprazolam, lorazepam, lormetazepam, medazepam, Metaclazapam, mexazolam, midazolam, nitrazepam, norazepam, Oxazepam, oxazolam, prazepam, temazepam, triazolam and / or their derivatives and / or their pharmaceutically acceptable Contain salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of weaning agents e.g. Nicotine, methadone, disulfiram, lobelin and / or their Derivatives and / or their pharmaceutically acceptable salts included as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of analgesics e.g. Ibuprofen, Ketoprofen, Alminoprofen, Bermoprofen, Carprofen, Dexibuprofen, dexketoprofen, fenoprofen, flobufen, Flunoxaprofen, flurbiprofen, loxoprofen, pelobiprofen, Pranoprofen, pentazocin, tilnoprofen, ximoprofen, Zaltroprofen, Diclofenac, Amfenac, Bromfenac, Clidanac, Etodolac, Felbinac, Fentiazac, Mofezolac, Oxindanac, Tifurac, Indomethacin, Acemetacin, Piroxicam, Ampiroxicam, Meloxicam, Isoxicam, Lornoxicam, Tenoxicam, Butorphanol Buprenorphine, morphine, hydromorphone, dihydrocodeine, Oxycodone, piritramide, pentazocin, levomethadone, tramadol, Fentanyl, codeine, codeine hydrochloride, codeine phosphate, Tilidine, Tilidine Mesylate, Tilidine Hydrochloride, Diclofenac Sodium, Amfenac sodium, bromfenac sodium, clidanac sodium, Etodolac sodium, felbinac sodium, fentiazac sodium, Mofezolac sodium, oxindanac sodium, tifurac sodium, Indomethacin sodium, acemetacin sodium, Meloxicam cyclodextrin, buprenorphine hydrochloride, Morphine acetate, hydromorphone hydrochloride, Oxycodone hydrochloride, piritramide hydrogen tartrate, Levomethadone hydrochloride, fentanyl dihydrogen citrate and / or their derivatives and / or their further pharmaceutical contain harmless salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of calcium antagonists e.g. Amlodipine, arandipine, azelmidipine, barnidipine, Benidipine, cilnidipine, efonidipine, felodipine, flordipine, Iganidipine, Isradipine, Lacidipine, Lercanidipine, Manidipine, Nicardipine, nifedipine, Nilvadipine, nisoldipine, nitrendipine, Palonidipine, pranidipine, ticlopidine, vatanidipine, clentiazem and / or their derivatives and / or their pharmaceutical contain harmless salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of antiemetics e.g. Alizapride, azasetron, batanopride, clebopride, dazopride, Dolasetron, Domperidon, Granisetron, Itasetron, Levosulpiride, metoclopramide, nabilone, ondansetron, Pancoprid, Ramosetron, Tropisetron, Zatosetron and / or their derivatives and / or their pharmaceutically acceptable Contain salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of vasodilators e.g. Glycerol trinitrate (nitroglycerin), isosorbide dinitrate, Isosorbide-5-mononitrate, pentaerythrityl tetranitrate, Molsidomine and / or their derivatives and / or their others pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of opiate antagonists z. B. naloxone, naltrexone and / or their derivatives and / or their pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of anticoagulants e.g. Heparin sodium, certoparin, dalteparin, danaparoid, Enoxaparin, nadroparin, reviparin, tinzaparin, heparinoids, Warfarin, phenprocoumon, acenocoumarol and / or their Derivatives and / or their pharmaceutically acceptable salts included as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of anti-Parkinson drugs e.g. Aptiganel, Biperiden, Budipin, Cabergolin, Droxidopa, Etacon, idazoxan, lazabemid, milacemid, mofegiline, Pergolide (pergolide mesylate, pergolide hydrochloride), Pramipexole, Quineloran, Rasagelin, Remacemid, Ropinorol, Selegiline, talipexole, tolcapone and / or their derivatives and / or their other pharmaceutically acceptable salts included as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of anti-dementia / cholinesterase inhibitors e.g. Rivastigmine, neostigmine, Physostigmine, pyridostigmine, donepezil, tacrine and / or their derivatives and / or their further pharmaceutical contain harmless salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of ACE inhibitors e.g. Alacepril, benazepril, captopril, ceronapril, cilazapril, Denapril, enalapril, enalapril maleate, fosinopril, imidapril, Lisinopril, Moexipril, Moveltipril, Perindopril, Quinapril, Ramipril, Ramiprilat, Ramipril Mesylate, Rentiapril, Spirapril, Temocapril, Trandolapril, Trandolapril Mesylate, Utibapril, Zofenopril and / or their derivatives and / or their other pharmaceutically acceptable salts as Active ingredient component included.

The transdermal therapeutic system can be one or several representatives from the group of antihistamines e.g. Acrivastine, astemizole, carebastine, cetirizine, Descarbethoxyloratadin, Dimetinden, Ebastin, Emedastin, Epinastine, fexofenadine, ketotifen, levocabastine, loratadine, Mequitazine, mizolastine, nafamostat, norastemizole, Olopatidine, oxatomide, rupatadine, tazifylline, temelastine, Traxanox and / or their derivatives and / or their others pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can include one or more representatives from the group of ulcer therapeutic / H ₂ receptor blockers, for example dalcotidine, famotidine, lafutidine, niperdidine, nizatridine, osutidine, pibutidine, pirenzepine, ramixotidine, ranitidine, proglumid, misoprostol and / or their derivatives and / or their derivatives and / or their derivatives or contain their pharmaceutically acceptable salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of angiotensin II antagonists e.g. Candesartan, candesartan cilexetil, Losartan, Tasosartan, Telmisartan, and / or their derivatives and / or their pharmaceutically acceptable salts as Active ingredient component included.

The transdermal therapeutic system can be one or several representatives from the group of neuroleptics e.g. Sulpiride, promethazine, benperidol, haloperidol, Chloroprothixes, clozapine, fluphenazine, perphenazine, Droperidol, pipamperon, prothipendyl, melperon, Flupentixol decanoate, fluspirils, bromperidol, Levomepromazine hydrogen maleate, zotepin, pimozide, perazine, Chlorprometazine, trifluprometazine, risperidone, sertindole, Amisulpride, olanzapine, zuclopenthixol, thioridazine and / or their derivatives and / or their pharmaceutically acceptable Contain salts as active ingredient.

The transdermal therapeutic system can be one or several representatives from the group of antidepressants e.g. Amitriptyline, clomopramine, maprotiline, doxepin, citalopram, Fluvoxamine, reboxetine, alprazolam, fluoxetine, lofepramine, Mianserin and / or their derivatives and / or their pharmaceutically acceptable salts as active ingredient contain.

The transdermal therapeutic system can be one or several representatives from the group of local anesthetics e.g. Lidocaine, Prilocaine, Benzocaine, Cocaine, Procaine, Tetracaine, Bupivacaine, Cinchocaine, Etidocaine, Mepivacaine, Butanilicain, Levobupivacaine, ropivacaine and / or their derivatives and / or their pharmaceutically acceptable salts as Active ingredient component included.

The transdermal therapeutic system can be one or several representatives from the group of lipid-lowering e.g. Colestyramine, xantinol nicotinate, fluvastatin, simvastatin, Atorvastatin, pravastatin, cerivastatin, dalvastatin, Itavastatin, Lovastatin, Dextrothyroxim Sodium and / or their derivatives and / or their pharmaceutically acceptable Contain salts as active ingredient.

That included in the transdermal therapeutic system Active ingredient can also e.g. Leflunomide, indapamide, Hydroxytamoxifene, fusidic acid, finasteride, tirofiban, Rosiglitazone, pioglitazone, montelukast and / or their Derivatives and / or their pharmaceutically acceptable salts his.

Pharmaceutically acceptable salts of the active ingredients mentioned are acid addition salts. This is obtained by the reaction of the active ingredient in the free form with pharmaceutically acceptable acids. Pharmaceutically acceptable acids are inorganic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid) or organic acids (e.g. acetic, propionic, hydroxyacetic, milk, pyruvic, oxalic, maleic, malonic, amber, Fumaric, apple, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic, p-aminosalicylic and pamoic acid). Solvates with the active ingredient are also referred to as acid addition salts. Such solvates are, for example, hydrates, alcoholates and the like.
Other possible pharmaceutically acceptable salts of the active substances mentioned are, in particular, alkali metal and / or alkaline earth metal salts and the ammonium salt, such as, for example, the potassium, sodium, lithium, calcium, magnesium and ammonium salt.

Figur 1 zeigt die Kaschierung der Deckfolie (3) bestehend aus Polymer, Kanalbildner und Absorptionsmittel auf das Laminat, das die selbstklebende Klebstoffmatrix (2) und die abziehbare Schutzschicht (1) enthält. Dabei wird das Laminat abgerollt (6) und mit Hilfe der Kaschierwalze (7) auf das Laminat aufgetragen.

Figur 2 zeigt die Auftragung der Mischung (5), bestehend aus Polymer, Kanalbildner und Absorptionsmittel, mit einem Walzenauftragsystem (8) auf die Oberseite der Deckfolie (4) sowie die anschließende Kaschierung mit der Kaschierwalze (7) der nun partiell mit der Mischung (5) beschichteten Deckfolie (4) auf das Laminat, das die selbstklebende Klebstoffmatrix (2) und die abziehbare Schutzschicht (1) enthält.

Figur 3 zeigt die Auftragung der Mischung (5), bestehend aus Polymer, Kanalbildner und Absorptionsmittel, mit einem Walzenauftragsystem (8) auf die Oberseite der Deckfolie (4), die ein Bestandteil des Laminates ist, das zudem die selbstklebende Klebstoffmatrix (2) und die abziehbare Schutzschicht (1) enthält. Im Anschluß an den Auftrag der Mischung erfolgt die Stanzung der Pflaster (9) und das Abgittern des Überstandes.

Figur 4 zeigt die Auftragung der Mischung (5), bestehend aus Polymer, Kanalbildner und Absorptionsmittel, mit einem Walzenauftragsystem (8) auf die Unterseite der Deckfolie (4) sowie die anschließende Kaschierung mit der Kaschierwalze (7) der nun partiell mit der Mischung (5) beschichteten Deckfolie (4) auf das Laminat, das die selbstklebende Klebstoffmatrix (2) und die abziehbare Schutzschicht (1) enthält.

Figur 5 zeigt die Auftragung der Mischung (5), bestehend aus Polymer, Kanalbildner und Absorptionsmittel, mit einem Walzenauftragsystem (8) auf die nach außen gerichtete Seite der abziehbaren Schutzschicht (1), die ein Bestandteil des Laminates ist, das zudem die selbstklebende Klebstoffmatrix (2) und die Deckschicht (4) enthält. Im Anschluß an den Auftrag der Mischung erfolgt die Stanzung der Pflaster (9) und das Abgittern des Überstandes.

Figur 6 zeigt eine Draufsicht auf das Laminat, das aus der Deckschicht (3), die mindestens ein Polymer, Kanalbildner und Absorptionsmittel enthält, der selbstklebenden Klebstoffmatrix (2) und der abziehbaren Schutzschicht (1) besteht und die verschiedenen Herstellungsschritte bis zum verpackten transdermalem therapeutischen System. Im Schritt A wird die Kontur des transdermalen therapeutischen Systems aus dem Laminat gestanzt. Schritt B zeigt die Entfernung des Überstandes. In Schritt C wird die Außenkontur des transdermalen therapeutischen Systems gestanzt. Schritt D zeigt das transdermale therapeutische System nach dem Abgittervorgang. E zeigt das transdermale therapeutische System mit aufgestanzter Abziehhilfe in dem Verpackungssachet (Durchsicht).

Figur 7 zeigt einen Querschnitt der erfindungsgemäßen Deckschicht (3) bzw. abziehbaren Schutzschicht (1) eines transdermalen therapeutischen Systems. Diese Deckschicht (3) bzw. abziehbare Schutzschicht (1) wird durch ein Polymer (16) gebildet, in dem die eingearbeiteten Kanalbildner eine Vielzahl von verzweigten Kanälen (14) bilden. Außerdem sind in dem Polymer Absorptionsmittelteilchen (15) gleichmäßig verteilt.

Figur 8 zeigt den Querschnitt durch ein Membransystem, welches aus der wirkstoffundurchlässigen Deckschicht (4), die mit der Mischung aus Polymer, Kanalbildner und Absorptionsmittel (5) partiell beschichtet ist, einem die Wirkstoffe enthaltenden Reservoir oder einer Reservoirschicht (12), einer für die Wirkstoffe durchlässigen Membran (11), einer Haftklebeschicht (10) und einer dem Stand der Technik entsprechenden abziehbaren Schutzschicht (1) besteht.

Figur 9 zeigt den Querschnitt durch ein Membransystem, welches aus der die Kanalbildner und Absorptionsmittel enthaltenden wirkstoffundurchlässigen Deckschicht (3), der herkömmlichen Deckschicht (4), einem die Wirkstoffe enthaltenden Reservoir oder einer Reservoirschicht (12), einer für die Wirkstoffe durchlässigen Membran (11), einer Haftklebeschicht (10) und einer dem Stand der Technik entsprechenden abziehbaren Schutzschicht (1) besteht.

Figur 10 zeigt den Querschnitt durch ein Matrixsystem, welches aus der die Kanalbildner und Absorptionsmittel enthaltenden wirkstoffundurchlässigen Deckschicht (3), einer die Wirkstoffe und gegebenenfalls Permeationsförderer enthaltenden Matrixschicht (13), einer Haftklebeschicht (10) und einer dem Stand der Technik entsprechenden abziehbaren Schutzschicht (1) besteht.

Figur 11 zeigt den Querschnitt durch ein Matrixsystem, welches aus der erfindungsgemäßen wirkstoffundurchlässigen Deckschicht (4), die mit der Mischung aus Polymer, Kanalbildner und Absorptionsmittel (5) partiell beschichtet ist, einer die Wirkstoffe und gegebenenfalls Permeationsförderer enthaltenden Matrixschicht (13), einer Haftklebeschicht (10) und einer dem Stand der Technik entsprechenden abziehbaren Schutzschicht (1) besteht.

Mono- and / or polyhydric aliphatic, cycloaliphatic and / or aromatic-aliphatic alcohols, each with up to eight carbon atoms, for example ethanol, 1,2-propanediol, dexpanthenol and / or polyethylene glycol, can optionally be used as permeation promoters. Alcohol / water mixtures; saturated and / or unsaturated fatty alcohols, each with 8-18 C atoms; terpenes; eg cineol, carveol, menthone, terpineol, verbenone, menthol, limonene, thymol, cymen, terpinen-4-ol, neomenthol, geraniol, fenchone; Mixtures of terpenes and ethanol and / or propylene glycol; tea tree oil; saturated and / or unsaturated cyclic ketones; Alkyl methyl sulfoxides; saturated and / or unsaturated fatty acids each with 8-18 C atoms; their esters and salts; natural vitamin E; synthetic vitamin E and / or vitamin E derivatives; Sorbitan fatty acid esters and ethoxylated sorbitan fatty acid esters; Azone (laurocapram); Azone mixed with alcohol; Urea; 1-alkylpyrrolidone; Block copolymers of polyethylene glycol and dimethylsiloxane with a cationic group at one end; Isopropyl myristate, isopropyl palmitate, folate-polyethylene glycol liposome, proliposome; Polyoxyethylene 10 stearyl ether; Mixture of polyoxyethylene 10 stearyl ether and glyceryl dilaurate; Dodecyl 2- (N, N-dimethylamino) propanol tetradecanoate and / or dodecyl 2- (N, N-dimethylamino) propianate; N-acetylprolinate esters with> 8 C atoms; nonionic surfactants, eg lauryl ether, esters of polyoxyethylene; Ethosome (phospholipid vesicle); Dimethyl (arylimino) sulfurane; Mixture of oleic acid analogs and propylene glycol; Mixture of Padimat O, octyl salicylate, octyl methoxycinnimate, laurocapram; highly disperse silicon dioxide (Aerosil®); Polyoxyethylene 7-glycerol monococoate (Cetiol® HE); Use 2-octyldodecanol (Eutanol® G) or a mixture of individual components.

Figure 1 shows the lamination of the cover film (3) consisting of polymer, channel former and absorbent on the laminate, which contains the self-adhesive matrix (2) and the removable protective layer (1). The laminate is unrolled (6) and applied to the laminate using the laminating roller (7).

Figure 2 shows the application of the mixture (5), consisting of polymer, channel former and absorbent, with a roller application system (8) on the top of the cover film (4) and the subsequent lamination with the laminating roller (7) which is now partially with the mixture ( 5) coated cover film (4) on the laminate, which contains the self-adhesive adhesive matrix (2) and the removable protective layer (1).

Figure 3 shows the application of the mixture (5), consisting of polymer, channel former and absorbent, with a roller application system (8) on the top of the cover film (4), which is a component of the laminate, which also the self-adhesive adhesive matrix (2) and the removable protective layer (1) contains. Following the application of the mixture, the plasters (9) are punched and the supernatant is trimmed off.

Figure 4 shows the application of the mixture (5), consisting of polymer, channel former and absorbent, with a roller application system (8) on the underside of the cover film (4) and the subsequent lamination with the laminating roller (7) which is now partially with the mixture ( 5) coated cover film (4) on the laminate, which contains the self-adhesive adhesive matrix (2) and the removable protective layer (1).

Figure 5 shows the application of the mixture (5), consisting of polymer, channel former and absorbent, with a roller application system (8) on the outward-facing side of the removable protective layer (1), which is a component of the laminate, which is also the self-adhesive adhesive matrix (2) and the cover layer (4) contains. Following the application of the mixture, the plasters (9) are punched and the supernatant is trimmed off.

Figure 6 shows a top view of the laminate, which consists of the cover layer (3), which contains at least one polymer, channel former and absorbent, the self-adhesive matrix (2) and the removable protective layer (1) and the various manufacturing steps up to the packaged transdermal therapeutic System. In step A, the contour of the transdermal therapeutic system is punched out of the laminate. Step B shows the removal of the supernatant. In step C, the outer contour of the transdermal therapeutic system is punched out. Step D shows the transdermal therapeutic system after the stripping process. E shows the transdermal therapeutic system with a pull-off pull-off aid in the packaging sachet (see through).

FIG. 7 shows a cross section of the cover layer (3) or removable protective layer (1) according to the invention of a transdermal therapeutic system. This cover layer (3) or removable protective layer (1) is formed by a polymer (16) in which the incorporated channel formers form a multiplicity of branched channels (14). In addition, absorbent particles (15) are evenly distributed in the polymer.

Figure 8 shows the cross section through a membrane system, which consists of the active ingredient-impermeable cover layer (4), which is partially coated with the mixture of polymer, channel former and absorbent (5), a reservoir containing the active ingredients or a reservoir layer (12), one for the Active substance permeable membrane (11), a pressure sensitive adhesive layer (10) and a peelable protective layer (1) corresponding to the prior art.

FIG. 9 shows the cross section through a membrane system which consists of the active substance-impermeable cover layer (3) containing the channel formers and absorbents, the conventional cover layer (4), a reservoir containing the active substances or a reservoir layer (12), a membrane (11) permeable to the active substances ), a pressure-sensitive adhesive layer (10) and a peelable protective layer (1) corresponding to the prior art.

FIG. 10 shows the cross section through a matrix system which consists of the active substance-impermeable cover layer (3) containing the channel formers and absorbents, a matrix layer (13) containing the active substances and possibly permeation promoters, a pressure-sensitive adhesive layer (10) and a removable protective layer corresponding to the prior art ( 1) exists.

FIG. 11 shows the cross section through a matrix system which, from the top layer (4) according to the invention which is impermeable to active substances and which is partially coated with the mixture of polymer, channel former and absorbent (5), comprises a matrix layer (13) containing the active substances and, if appropriate, permeation promoters, a pressure-sensitive adhesive layer (10) and a removable protective layer (1) corresponding to the prior art.

The invention is further illustrated by the following examples explains without but the scope of the invention limit.

example 1 :

Production of an active ingredient-impermeable Top layer or removable protective layer of a transdermal therapeutic system in the form of a film:

First the components polymer, channel formers and Absorbent mixed at elevated temperature, where preferably a premix of polymer and channel former he follows.

The mixture is heated to melt and over usual Process (state of the art) in casting or Blown extrusion process processed into a film. While processing may be necessary Manufacturing area related to the surrounding atmosphere partially or completely to condition (especially reduced RH, reduced 02 content) for example through use dried protective gases. Following this The manufacturing process may require additional stretching of the films to modify the mechanical properties and Reduction in thickness can be made. This Manufacturing process can be found in the prior art.

The film thus obtained can be stored in a suitable manner become. It serves to cover a pressure sensitive adhesive equipped layer containing the active substance that already on one side with a release-coated or with a Separating coating provided carrier material is covered. Possibly. can initially also use this material on both sides release coated carrier materials may be provided, wherein a support layer immediately before joining with the above-mentioned Film must be removed (laminate). Farther the intermediate layer can consist of several layers, whereby contains at least one of these layers of active ingredients. So is one Laminate made of release-coated film, more active ingredient Layer or layers and desiccant layer receive. This laminate is made by punching, cutting or other suitable methods a single dose generated, which is temporarily stored under suitable conditions or is packed directly. Again, during the Processing or intermediate storage may be required the manufacturing area related to the surrounding atmosphere partially or completely to condition (especially reduced RH, reduced 02 content), for example through use dried protective gases.

Example 2:

Making one with an absorbent and Coating channel-forming polymer carrier Active ingredient-permeable cover layer or removable protective layer of a transdermal therapeutic system

First the components polymer, channel formers and Absorbent mixed at elevated temperature, where preferably a premix of polymer and channel former he follows.

The mixture obtained is portioned for a later one Packaged for further processing or processed directly. The mixture is melted, e.g. in an extruder or via other suitable mixing and / or dosing devices, such as for example in the basic versions Hot melt adhesive application are common. Following is the mixture e.g. by nozzle or roller application on one Foil that is already part of the compound containing the active ingredient or is defined in quantity and / or position applied. A dosage to that is preferred drug-impermeable cover layer of a drug-containing Verbund immediately before the manufacture and packaging of the Single dose. Again, it can be during processing or intermediate storage may be required Manufacturing area related to the surrounding atmosphere partially or completely to condition (especially reduced RH, reduced 02 content), for example through use dried protective gases.

Example 3:

Composition of the mixture: polypropylene 70% by weight polyethylene glycol 10% by weight Molecular sieve 4Å 20% by weight

Example 4:

Composition of the mixture: polypropylene 35% by weight polyethylene glycol 12% by weight Molecular sieve 4Å (Baylith® T powder) 53% by weight

Example 5:

Composition of the mixture: polyethylene 55% by weight polyethylene glycol 10% by weight Molecular sieve 4Å 35% by weight

Claims (34)

1. A cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system, wherein the cover layer and/or protective layer is characterized by a mixture of at least one polymer and at least one embedded absorbing agent and at least one embedded channel-forming agent.
2. The cover layer that is impermeable to the active substances in the form of a film and/or a removable protective layer in the form of a film of a transdermal therapeutic system, characterized in that the film is coated with a mixture of at least one polymer, at least one channel-forming agent, and at least one absorbing agent, over the entire surface or in patterns.
3. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claims 1 or 2, characterized in that a thermoplast or a crosslinkable or crosslinked polymer, respectively, is the polymer in the mixture of the polymer, absorbing agents, and channel-forming agents.
4. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claims 2 or 3, characterized in that the cover layer and/or the protective layer have been coated with a mixture (polymer support) consisting of at least one thermoplast, at least one channel-forming agent, and at least one absorbing agent.
5. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claims 2 or 3, characterized in that the cover layer and/or the protective layer have been coated, whether in a cold or hot state, with a mixture (polymer support) consisting of

   (i) at least one thermally crosslinkable polymer, at least one channel-forming agent, and at least one absorbing agent, or

   (ii) at least one polymer which can be crosslinked by means of radiation, in particular UV radiation, at least one channel-forming agent, and at least one absorbing agent, and

   in either case, the crosslinking has been performed thereinafter.
6. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with one of the preceding Claims, characterized in that the polymer is a polyolefin, polyisoprene, polybutadiene, polybutene, polysiloxane, polyamide, ethylene vinyl acetate copolymer, ethylene methacrylate copolymer, polystyrene, polyester, polyanhydride, polyacrylate nitrile, polyacryl nitrile, polysulfonate, polyesteramide, polyacrylate ester, propylene maleic anhydride, polyethylene maleic anhydride, polyethylene urethane, polyethylene ethyl vinyl alcohol, polyethylene nylon, and/or polyurethane.
7. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claim 6, characterized in that the polymer is polyethylene and/or polypropylene.
8. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with one of the preceding Claims, characterized by a polymer content of 10 to 90 percent by weight, based on the total weight of the mixture of the polymer, channel-forming agents, and absorbing agents.
9. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with one of the preceding Claims, characterized in that the channel-forming agents are hydrophilic substances.
10. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with Claim 9, characterized in that the channel-forming agents are polyglycols, ethyl vinyl alcohols, glycerin, pentaerythritol, polyvinyl alcohols, polyvinyl pyrrolidone, vinyl pyrrolidone, N-methyl pyrrolidone, polysaccharides, saccharides, and/or sugar alcohols.
11. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claim 10, characterized by

    polyethylene glycol and/or polypropylene glycol as a polyglycol, and/or

    glucose, mannose, galactose and/or fructose as a saccharide, and/or

    mannitol, sorbitol, hexitol, dulcitol, xylitol, ribitol and/or erythrol as a sugar alcohol.
12. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with Claim 9, 10, or 11, characterized by a content of the channel-forming agents of 10 to 40 percent by weight based on the total weight of the mixture of the polymer, channel-forming agents, and absorbing agents.
13. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with one of the preceding Claims, characterized in that the absorbing agent is a substance for the absorption of humidity, oxygen or of substances which are released by a transdermal therapeutic system during storage, in particular of highly odorous substances, especially amines or polymer monomers.
14. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with one of the preceding Claims, characterized in that the absorbing agents are drying agents, metals, alloys, metal-coated particles, inorganic substances, ion-exchange resins, substances on the basis of carbon, in particular on the basis of elemental carbon, elastomers, semi-metals, and/or ceramic materials.
15. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with Claim 14, characterized in that the physical drying agents include molecular sieves, silicon gels, earths, synthetic polymers and/or starches, in particular molecular sieves.
16. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claim 15, characterized in that montmorrillimite earth or montmorrillonite earth or polymers that are used in baby diapers or molecular sieves with a pore size from 3 to 15 Å or silicon dioxide gel with a pore size of approx. 24 Å are used, as drying agents.
17. The cover layer that is impermeable to the active substances and/or a removable protective layer in accordance with Claim 14, characterized in that

    nickel, copper, aluminum, silver and/or gold are used as a metal or alloy,

    silver-coated copper, silver-coated nickel, and/or silver-coated glass microspheres are used as metal-coated particles,

    barium titanium trioxide, strontium titanium trioxide, silicon dioxide, aluminum oxide, zinc oxide, titanium dioxide, manganese oxide, copper oxide, antimony oxide, molten or melted silicon, amorphous molten or amorphous melted silicon, ion-exchange resins, lithium-containing metal oxides, hollow glass microspheres, silicon sol-gel, titanium sol-gel, and/or mixed titanium are used as inorganic substances,

    carbon, activated charcoal and/or diamond powder are used as carbon-based substances, and/or

    polybutadiene and/or polysiloxanes are used as elastomers.
18. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with Claims 14 or 15, characterized by a content of the absorbing agent from 10 to 70 percent by weight based on the total weight of the mixture of the polymer, channel-forming agents, and absorbing agents.
19. The cover layer that is impermeable to the active substances and/or a removable protective layer of a transdermal therapeutic system in accordance with at least one of Claims 1 and 3 through 18, characterized by a layer thickness of 5 to 100 µm, in particular 15 to 40 µm, preferably 15 µm.
20. The cover layer that is impermeable to the active substances (and/or a removable protective layer) of a transdermal therapeutic system in accordance with one of Claims 2 through 19, characterized in that the film used for the cover layer that is impermeable to the active substances is coated with the mixture on its top side and/or bottom side.
21. The (cover layer that is impermeable to the active substances and/or a) removable protective layer of a transdermal therapeutic system in accordance with one of Claims 2 through 19, characterized in that the film that is used for the removable protective layer is coated with the mixture on its outward-facing side.
22. A transdermal therapeutic system in the form of a matrix system or membrane system, characterized by a cover layer that is impermeable to the active substances and/or a removable protective layer consisting of a mixture of at least one polymer and an embedded absorbing agent and channel-forming agent.
23. The transdermal therapeutic system in accordance with Claim 22, characterized by a cover layer and/or a protective layer in accordance with one of Claims 1 or 3 through 21.
24. The transdermal therapeutic system in the form of a matrix system or membrane system, characterized by a cover layer that is impermeable to the active substances and/or a removable protective layer comprising a film that has been coated with a mixture (polymer support) of at least one polymer, channel-forming agents, and absorbing agents over its entire surface or in patterns.
25. The transdermal therapeutic system in accordance with Claim 24, characterized by a cover layer and/or a protective layer in accordance with one of Claims 2 through 21.
26. The transdermal therapeutic system in accordance with one of Claims 22 through 25, characterized in that the system is a matrix system with

    a cover layer that is impermeable to the active substances,

    one or more active substance-containing self-adhesive matrix layer(s) or one or more active substance-containing matrix layer(s) that have been coated with a pressure-sensitive adhesive, and

    a removable protective layer.
27. The transdermal therapeutic system in accordance with one of Claims 22 through 25, characterized in that such system is a membrane system with

    an impermeable cover layer,

    an active substance-containing reservoir or an active substance-containing reservoir layer,

    a microporous or semipermeable membrane, and

    an optional pressure-sensitive adhesive layer.
28. A method for the manufacture of a transdermal therapeutic system with a layer that is impermeable to the active substances and a removable protective layer, characterized in that a polymer support containing absorbing agents and channel-forming agents is applied, over the entire surface or in patterns, to the cover layer that is impermeable to the active substances and/or the removable protective layer.
29. The method in accordance with Claim 28, characterized in that the top side and/or the bottom side of the cover layer that is impermeable to the active substances is coated with the polymer support.
30. The method in accordance with Claims 28 and/or 29, characterized in that the outside of the removable protective layer is coated with the polymer support.
31. The method for the manufacture of a transdermal therapeutic system with a cover layer that is impermeable to the active substances and a removable protective layer, characterized in that absorbing agents and channel-forming agents are incorporated in the cover layer that is impermeable to the active substances and/or the removable protective layer.
32. The method in accordance with one of the preceding Claims, characterized in that, as a transdermal therapeutic system, a matrix or membrane system is produced.
33. The method in accordance with Claim 32, characterized in that a transdermal therapeutic system with one or more self-adhesive matrix layers is produced.
34. The method in accordance with at least one of Claims 28 through 32, characterized in that a transdermal therapeutic system with one or more matrix layers is produced which are coated with a pressure-sensitive adhesive.